Breast cancer (BC) is the most common female cancer and the first leading cause of cancer death in women. Luminal phenotypes represent about 70% of this disease. Treatment for metastatic hormone-dependent HER2-negative breast cancer in most cases involves various lines of endocrine therapy since their sequential use improves overall and relapse-free survival while maintaining a high quality of life. Disease progression during such therapy may be associated with the development of primary or secondary resistance to the treatment. The reason for the secondary resistance is both a mutation of receptors for steroid hormones and activation of new signaling pathways. The study of these mechanisms has led to the creation of highly effective drug combinations for the treatment of hormone-positive HER2-negative metastatic breast tumors. To date, clinical trials of three agents from the group of cyclin-dependent kinases has been developed and successfully completed: palbociclib, ribociclib and abemaciclib. These agents in combination with non-steroidal aromatase inhibitors or estrogen receptor antagonists in randomized clinical trials increased direct treatment efficacy, overall survival and progression-free survival rates. Clinical case of a menopausal patient with metastatic hormone-positive HER2-negative breast cancer with visceral metastases who received successive chemotherapy and a combination of the highly selective oral kinase inhibitor CDK4\6 ribocyclib with the aromatase inhibitor letrozole allowed to achieve a response to therapy for 27 months with CR for 8 months. The safety profile was satisfactory; side effects included grade 2 neutropenia, grade 1 arthralgia, grade 1 hyperglycemia and grade 1 increase in urea which did not had an adverse effect on the patient's quality of life.
The development of a new direction in anticancer medical therapy – the use of immune checkpoint inhibitors targeting PD-1/ PD-L1 and CTLA-4 – has significantly changed the approach to tumor treatment in the last few years. The PD1 blocker nivolumab in major registered clinical trials improved overall survival, including in metastatic melanoma, with a favorable toxicity profile. However, its efficacy in patients with brain metastases from melanoma was poorly studied, since the inclusion criteria for most clinical trials do not envisage recruiting such patients. The immune-mediated toxicity of immune checkpoint inhibitors is currently well enough studied. However, cases of cutaneous toxicity are quite rare and present certain difficulties for differential diagnosis and treatment. This article presents two cases of effective nivolumab treatment in patients with generalized BRAFwt and BRAFmut cutaneous melanoma. The first case is of interest due to the presence of brain metastases in the patient. Nivolumab therapy helped achieving complete regression of intracranial metastases with the long-term effect. The second case, in addition to effective treatment, demonstrates a rare manifestation of skin toxicity – vitiligo on the face and upper extremities.
Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein‑4 (CTLA‑4) and programmed cell death protein‑1 (PD‑1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.
Introduction. Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients.The purpose of study. Clinical evaluation of the efficacy and safety of Eralfon® (epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy.Materials and methods. We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed.Results. Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia.Conclusion. Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.
Purpose of the study. An analysis of changes in the expression of the VEGF neoangiogenic factor in the tumor tissue of patients with squamous cell carcinoma of the oral mucosa receiving targeted therapy with cetuximab and chemotherapy.Patients and methods. We performed an immunohistochemical study of tumor samples obtained from 60 patients with squamous cell carcinoma of the oral mucosa T3-4N0-1M0. The main group comprised 30 patients who received therapy with cisplatin and fluoruracil plus cetuximab. The control group included 30 patients receiving standard chemotherapy without targeted therapy. Each group was divided into two subgroups with different treatment efficacy: patients sensitive to treatment (n = 17 in the group with cetuximab and n = 12 in the group without cetuximab) and resistant to treatment (n = 13 in the group with targeted therapy and n = 18 in the group with standard chemotherapy).Results. Quantification of the VEGF expression demonstrated minimal numbers of vessels stained positively for this marker in the field of view in patients of the main group sensitive to chemotherapy and cetuximab. The value was 5.3 times lower than initial values, and 4.3 times lower than in the subgroup of patients resistant to the treatment (the data were statistically significant, р = 0.0132 and р = 0.0455, respectively). In the control group, patients who were sensitive to the treatment showed 1.4 times lower values than initially (р = 0.921), and patients who were resistant to the treatment had 1.1 times lower values than initial values (р = 0.936). The data were not statistically significant.Conclusions. The study showed that the number of microvessels in patients resistant to chemotherapy and cetuximab was 4.3 times higher than in patients with effective targeted therapy (р = 0.0455). The differences in the control group were not statistically significant.
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